Anti-inflammatory effects of ginsenoside Rg3 on the hypertrophic scar formation via the NF-κB/IκB signaling pathway in rabbit ears.

The anti-inflammatory effects of Rg3 on the hypertrophic scar (HS) formation remain relatively obscure. Hence, this study aimed to explore the anti-inflammatory effects of Rg3 on the HS formation using a rabbit ear model and we assessed the involvement of the NF-κ B/IκB signaling pathway in this process. We constructed the Newland white rabbit ear HS model and treated it with Rg3. Using histological analyses, we evaluated scar hypertrophy based on the hematoxylin and eosin staining. The degree of scarring was evaluated using the scar elevation index (SEI). In addition, collagen I and collagen III expression levels were assessed by immunohistochemistry, while fibroblast apoptosis was examined using TUNEL assays. While MPO, IL-1ß, IL-6, and TNF-α concentrations were quantified using ELISA, NF-κB and p-IκB activities were respectively measured using electrophoretic mobility shift assays (EMSAs) and western blots. SEI measurements and histological characteristics revealed that Rg3 could suppress the HS formation. Moreover, Rg3 could inhibit the HS formation by decreasing collagen I and collagen III synthesis and inducing fibroblast apoptosis. Besides, Rg3 treatment markedly inhibited the inflammatory cytokine production and ameliorated neutrophil infiltration. Notably, this study revealed that Rg3 inhibited NF-κB activation and the activity of p-IκB. Furthermore, this study suggested that the ability of Rg3 to decrease the scar formation might result from its ability to inhibit inflammation by modulating the NF-κB/IκB signaling. Overall, the findings of this study could support the use of Rg3 to prevent the HS formation.

High eukaryotic translation elongation factor 1 alpha 1 expression promotes proliferation and predicts poor prognosis in clear cell renal cell carcinoma.

Accumulating evidence indicates that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) is involved in cancer, while the clinical significance and the exact role of eEF1A1 in renal cell carcinoma (RCC) remain obscure. The aim of the present study was to evaluate the clinical significance of eEF1A1 in RCC and to investigate its effective mechanisms in order to identify a potential therapeutic target. The expression levels of eEF1A1 in RCC were explored by immunohistochemistry in tissues from 184 patients. eEF1A1 was knocked down, and cell proliferation and apoptosis were then investigated. The MAPK pathway-related proteins were detected by western blot. Our results revealed that eEF1A1 was highly expressed in RCC tissues and associated with poor prognosis. Knockdown of eEF1A1 attenuated proliferation and promoted the apoptosis of RCC cells. Furthermore, eEF1A1 knockdown decreased the phosphorylation level of AKT and ERK. In conclusion, eEF1A1 may serve as a valuable prognostic biomarker and promising therapeutic target of RCC.

GRK5 promotes tumor progression in renal cell carcinoma.

GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Here, we report an important tumor-promoting role for GRK5 in renal cell carcinoma (RCC). We investigated the expression pattern, clinical significance, and function of GRK5 in RCC. By using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), we first demonstrated that compared with paired adjacent nontumor (NT) tissues, RCC tissues presented with higher GRK5 expression. Moreover, we found that GRK5 upregulation was associated with poor clinical outcomes in RCC patients. In vitro, we found that GRK5 knockdown reduced viability, invasive ability, migratory ability, and decreased proportion of cells in S phase, with concomitant increase in G1 phase in RCC cell lines, while GRK5 overexpression promoted tumor cell proliferation, cell invasion, migration and increased proportion of cells in S phase, with concomitant decrease in G1 phase. Collectively, our findings describe the tumour-promoting role of GRK5 in RCC and thus provide molecular evidence for new therapeutic options in RCC.

The effects of recombinant human growth hormone (rHGH) on survival of slender narrow pedicle flap and expressions of vascular endothelial growth factor (VEGF) and classification determinant 34 (CD34).

OBJECTIVE: To explore the effects of recombinant human growth hormone (rHGH) on the survival of the mouse slender narrow pedicle flap and the expressions of vascular endothelial growth factor (VEGF) and classification determinant 34 (CD34). MATERIALS AND METHODS: A total of 20 BALB/c mice were randomly divided into the experimental group (n=10) and control group (n=10). The flaps were transplanted for mice in two groups respectively. 6 h after the operation, the mice in the experimental group were administrated with rHGH via local subcutaneous injection, while the mice in the control group were injected with the same amount of normal saline. The laser Doppler was used to measure the sub-flap blood flow rates before the operation, and 3 days, 7 days and 14 days after the operation, respectively; the flap necrosis and survival areas of mice in two groups were measured respectively, and the survival rate of the flap was calculated 14 days after the operation. Afterwards, the flaps of mice in two groups were exfoliated and the shape and structure of flap tissues were tested by the hematoxylin-eosin (HE) staining. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to test the levels of mRNA and protein of VEGF and CD34 in the flap tissues. RESULTS: The flaps of mice in the control group mainly exhibited the black or grayish-black and lost the elasticity with the hard texture, while those in the experimental group were ruddy in color with favorable elasticity. The survival rate of flaps of mice in the experimental group was significantly higher than that in the control group (83.61 ± 12.56% vs. 46.25 ± 9.70%) and the necrosis area of flaps of mice in the experimental group was significantly smaller than that in the control group (1.32 ± 0.16 vs. 4.13 ± 0.35, p < 0.05). There were no statistical differences in the blood flow rates of mouse flap both before the operation and three days after the operation between two groups (p > 0.05), while the blood flow rates of mouse flap both 7 days and 3 days after the operation in the experimental group were higher than those in the control group (p > 0.05). Compared with those in the control group, the levels of VEGF and CD34 were significantly increased, but the levels of the inflammatory factors of the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly decreased (p < 0.05). CONCLUSIONS: rHGH plays an active role in the survival of the flap through promoting the angiogenesis and inhibiting inflammatory reaction.

Adipose-derived stem cells improve neovascularization in ischemic flaps in diabetic mellitus through HIF-1α/VEGF pathway.

OBJECTIVE: To investigate the improvement effect of adipose-derived stem cells on neovascularization in an ischemic flap in diabetes mellitus (DM), and to explore the mechanism of hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were divided into control group, model group, and adipose-derived stem cells (ADSCs) group. The survival rate of the flap and the number of new blood vessels were measured. The content of VEGF was determined by enzyme-linked immunosorbent assay (ELISA) kit. Then, the expressions of HIF-1α and VEGF in each group were measured by immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) method and Western blotting assay were used to detect the mRNA and protein expression of HIF-1α and VEGF in each group. RESULTS: Compared with control group, the flap survival rate of model group was decreased significantly, and the number of new blood vessels was also decreased significantly. Compared with model group, the flap survival rate of ADSCs group was increased significantly, and the number of new blood vessels was also increased significantly. The results of ELISA showed that compared with control group, the level of VEGF in model group was lower than that in model group, and the level of VEGF in the ADSC group was significantly higher than that in the model group. IHC results showed that both HIF-1α and VEGF proteins were decreased significantly in model group, whereas the expression of HIF-1α and VEGF in the ADSCs group was increased significantly. The results of RT-PCR and the Western blotting showed the mRNA and protein expressions in model group were all decreased, while those in ADSCs group were significantly increased (p < 0.05). CONCLUSIONS: ADSCs can improve the neovascularization of diabetic ischemic skin by regulating the HIF-1α/VEGF pathway.

Confirmation and refinement of a genetic locus for disseminated superficial actinic porokeratosis (DSAP1) at 12q23.2-24.1.

BACKGROUND: Our previous study has identified two loci for disseminated superficial actinic porokeratosis (DSAP), but the genes responsible are still unknown. OBJECTIVES: To narrow down the candidate regions and to assess candidate genes. METHODS: A genome-wide scan and linkage analysis were carried out in a newly collected five-generation Chinese family with DSAP. In addition, six candidate genes were screened for possible DSAP-associated mutations. RESULTS: DSAP in this family was associated with chromosome 12q. Fine mapping and haplotype construction refined the DSAP1 locus to a 4.4-cM interval. No disease-associated mutation was detected in CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 or KIAA0789 genes. CONCLUSIONS: The DSAP1 locus was localized to a 4.4-cM interval at chromosome 12q23.2-24.1. CRY1, C4ST1, TXNRD1, HCF2, CMKLR1 and KIAA0789 genes were not associated with DSAP1.

Facial subdermal vascular network flap: anatomic study and clinical application.

Despite the numerous flaps for facial reconstruction that have been described, the search for the ideal flap with good color matching and minimal donor-site morbidity continues. In the past 3 years we have repaired 13 facial defects with success using the lateral genicervical flap - a type of facial subdermal vascular network flap (SVNF) - with a pedicle located on the preauricular region. An anatomic study of the facial SVNF, including blood supply and vascular distribution of the face and anatomic characteristics of facial vessels, based on 14 cadaver dissections, was carried out. The blood supply of the facial skin basically originated from the branches of the facial, superficial temporal and infraorbital arteries. The lateral genicervical skin was supplied basically by the branches of the facial, superficial temporal and occipital arteries, but also by the terminal branches of the superior thyroid artery. The branches diverging from these arteries became superficial and formed a subcutaneous arterial network. The arterioles from the network went to the corium layer and formed a subdermal arterial network whose arterioles anastomosed with each other in a honeycomb-like structure. The vascular distribution presented certain directivity on different areas. The blood supply of the pedicle originated from the subdermal vascular network formed by the perforator branches of these arteries. The arterioles from the facial and superficial temporal arteries anastomosed in the lateral genicervical region. From the anatomic study, we think that the viability of the facial SVNF depends basically on the subdermal vascular network formed by the perforator branches of the pedicle, and that the anastomoses between the facial and superficial temporal arteries provide a solid anatomic basis to the lateral genicervical flap. The clinical data also indicated that this flap is a useful alternative for facial, especially superficial temporal, defects. But the directivity must be taken into account in its clinical application.